Traumatic brain injury (TBI) contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) is upregulated and reduces CBF after fluid percussion brain injury (FPI) in piglets. We hypothesized that increased CPP via phenylephrine (PHE) sex dependently reduces impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK.
Prospective, randomized animal study.
Newborn (1–5 day old) pigs.
CBF, pial artery diameter, ICP and autoregulatory index (ARI) were determined before and after FPI in untreated, pre- and post-injury PHE (1 μg/kg/min iv) treated male and female pigs during normotension and hemorrhagic hypotension. CSF ERK MAPK was determined by ELISA.
Measurements and Main Results
Reductions in pial artery diameter, CBF, CPP and elevated ICP after FPI were greater in males, which were blunted by PHE pre- or post-FPI. During hypotension and FPI, pial artery dilation was impaired more in males. PHE decreased impairment of hypotensive pial artery dilation after FPI in females, but paradoxically caused vasoconstriction after FPI in males. Papaverine induced pial artery vasodilation was unchanged by FPI and PHE. CBF, CPP, and ARI decreased markedly during hypotension and FPI in males but less in females. PHE prevented reductions in CBF, CPP, and ARI during hypotension in females but increased reductions in males. CSF ERK MAPK was increased more in males than females after FPI. PHE blunted ERK MAPK upregulation in females, but increased ERK MAPK upregulation in males after FPI.
These data indicate that elevation of CPP with PHE sex dependently prevents impairment of cerebral autoregulation during hypotension after FPI through modulation of ERK MAPK. These data suggest the potential role for sex dependent mechanisms in cerebral autoregulation after pediatric TBI.